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1 Asbestos exposure and asbestos-related diseases in Croatia Esposizione ad amianto e malattie ad esso correlate in Croazia Marko Šarić Institute for Medical Research and Occupational Health, Zagreb, Croatia Summary After a short description of the first cases of asbestosis in Croatia diagnosed in workers from an asbestos-cement factory (1960) and information about asbestosis incidence in the country during the last decade, the paper deals with the occurrence of malignant tumours due to occupational and/or environmental exposure to asbestos. The results of three epidemiological studies on respiratory and gastrointestinal tract tumours in areas with an asbestos processing plant (1994), and an asbestos-cement plant (1995 and 1996) are summarized. In recent years the emphasis has been put on malignant pleural mesothelioma. A clinical study related to this tumour was carried out in Dalmatia and the results were presented in A recent epidemiological study published in 2002 dealt with the incidence of the same tumour in Croatia. This study showed that the rates of malignant pleural mesothelioma were significantly higher in people in the coastal area compared with the rest of the country. More than two thirds of patients with the tumour were occupationally exposed to asbestos. This uneven distribution of the tumour rates is presumably related to shipbuilding and other industrial sources of asbestos exposure located in the coastal region of Croatia. Sources of environmental exposure to asbestos have also to be considered. The last part of the paper contains information about asbestos consumption and legislation in the country, and discusses briefly the problem and timing of an asbestos ban in view of Croatia s intention to join the European Union. Key words: asbestos, asbestosis, mesothelioma, Croatia Riassunto Dopo una breve descrizione dei primi casi di asbestosi in Croatia, diagnosticati tra i lavoratori di un industria del cemento-amianto (1960) e dei dati sull incidenza di asbestosi nel paese nell ultimo decennio, il lavoro tratta l insorgenza di tumori maligni da esposizione professionale e/o ambientale ad amianto. Vengono riassunti i risultati di tre studi epidemiologici sui tumori degli apparati respiratorio e gastroin- Address/Indirizzo: Dr. Marko Šarić, Institute for Medical Research and Occupational Health, Zagreb, Croatia 17

2 Eur. J. Oncol. Library, vol. 3 testinale in aree con un impianto per la lavorazione dell amianto (1994) ed una fabbrica di cemento-amianto (1995 e 1996). Negli ultimi anni è stata sottolineata l importanza del mesotelioma maligno della pleura. In Dalmazia è stato condotto uno studio clinico su questo tumore, i cui risultati sono stati presentati nel Un recente studio epidemiologico pubblicato nel 2002 riguarda l incidenza dello stesso tumore in Croazia. Questo studio ha dimostrato che i tassi di mesotelioma maligno della pleura erano significativamente più alti nella regione costiera rispetto al resto del paese. Più di due terzi dei pazienti con tumore erano stati esposti professionalmente ad amianto. Questa distribuzione disomogenea dei tassi tumorali è probabilmente collegata ai cantieri navali e ad altre sorgenti industriali di esposizione ad amianto, situati nella regione costiera della Croazia. Devono essere valutate anche le fonti di esposizione ambientale ad amianto. L ultima parte del lavoro contiene dati sul consumo di amianto e sulla legislazione del paese, e discute brevemente il problema ed il momento opportuno di una messa al bando dell amianto, considerata l intenzione della Croazia di entrare nell Unione Europea. Parole chiave: amianto, asbestosi, mesotelioma, Croazia Asbestosis in Croatia In Croatia, exposure to asbestos and its adverse health effects were first objectively studied in a health survey of an asbestos-cement plant in All workers, 48 men and 16 women, were clinically examined and submitted to X-ray examination. Measurements of dust concentration were also carried out. Asbestosis in various stages was observed in 6 workers (four men and two women). None of the affected workers had worked in the plant for less than 5 years. In fact, they all belonged to a group with the longest and severest exposure to asbestos. This small study showed that asbestosis could occur in factories manufacturing asbestos products. Until then, reports of asbestosis in the former Yugoslavia were limited to the extracting industry. In addition to asbestos-cement production, later cases of asbestosis were diagnosed in the shipbuilding and asbestos processing industries. From 1990 to 2000, 317 cases of asbestosis as an occupational disease were reported in Croatia: 289 with parenchymal fibrosis and the rest with parenchymal and pleural changes, or pleural plaques/calcifications only 2. Studies on tumour incidence in areas with asbestos processing plants Early interest was focussed on the occurrence of malignant tumours in occupational as well as environmental exposure to asbestos. The incidence of malignant tumours of the lung/bronchus, pleura, larynx, pharynx, and peritoneum was studied in a coastal area of Croatia with an asbestos processing plant 3. The area covered 169 km 2, and the study included 11,300 inhabitants: 5,590 men and 5,710 women (average number during the study period). Over the observed period ( ) there were 51 cases of malignant tumour (40 in men and 11 in women). Table 1 shows the number of tumours and their distribution by occupation. The incidence of lung/bronchus cancer in the studied area population was almost half the expected total in Croatia as a 18

3 M. Šarić: Asbestos-related diseases in Croatia Table 1 - Malignant tumours in the area with an asbestos processing plant by occupation Primary sites Occupation Lung and bronchus Pleura Larynx Pharynx Peritoneum Asbestos factory worker 2 Construction worker 3 Farmer Other Housewife Total whole. The incidence of primary tumours of the pleura was five times higher and of laryngeal tumours twice as high as in Croatia as a whole (Table 2). Two cases of malignant pleural mesotheliomas were found in workers from the asbestos-processing plant, but none of the lung/bronchus tumour cases were associated with occupational exposure. A more detailed analysis of data obtained in the study indicated that the terrain and the prevailing wind may have influenced the environmental contamination with asbestos from the emission source and consequently may have produced an uneven distribution of the tumour incidence among settlements in the studied area. It was interesting to note that tumours were rather frequent in subjects who worked outside, in the open air. Farmers comprised 39% of those with observed tumours. Another study dealt with the incidence of cancer of the lung, pleura, larynx and pharynx in the area with the asbestos-cement plant 4. Data on persons who died of these types of cancer were collected and analysed for the period Cancer mortality data were obtained from the Cancer Registry of Croatia. Additional data on occupation, lifestyle (smoking, alcohol drinking), length of residence in the area, educational level were collected from the relatives of the deceased. According to the census data from 1981, the study area had 235,922 inhabitants: 115,255 men and 120,667 women. The results of the investigation showed that the mortality rates for the lung, larynx and pharynx cancers, standardised according to age, were lower in the study area than expected (data for Croatia). Standardised mortality rates for mesothelioma were higher for both sexes, except for women in the rural part of the area, than in the rest of Croatia (Table 3). The highest follow-up cancer mortality rates were registered in the settlement where the asbestos-cement plant was located. Some settlements in two municipalities within the area also had higher mortality rates caused by these tumours in comparison with the rest of the study area or Croatia as a whole. Table 2 - Annual incidence rates (per 100,000) of malignant tumours in persons aged 35 years and older for the area with the asbestos factory and for Croatia as a whole Tumour primary site Average incidence Asbestos factory area Croatia M F Total M F Total Lung/bronchus Pleura Larynx Pharynx Peritoneum

4 Eur. J. Oncol. Library, vol. 3 Table 3 - Age standardized (30 years and older) death rates/100,000 of malignant tumours of the pharynx, larynx, lung and pleura in the study area and in Croatia as a whole (period ) a Tumour site Subareas in the study area Croatia Split Solin Kaštela Zagora Total Pharynx ( ) Men 5.0** * 6.8 Women Total 2.6* Larynx (161) Men 9.6*** *** 15.7 Women Total 5.2*** *** 7.8 Lung (162) Men 93.7*** ** 98.9*** Women * Total 53.6*** *** 55.2*** 63.9 Pleura (163) Men * ** 1.8 Women Total 2.4* 5.6* *** 1.4 a For statistical analysis comparison of Poisson rates (Statgraphic 3.0, USA, 1988) was used *p <0.05, ** p<0.01, *** p <0.001 The evaluation of the findings took into consideration the possibility of uneven distribution of emissions from the asbestos-cement plant caused by prevailing winds. With reference to the cumulative number and average annual death rates (per 100,000 inhabitants) due to malignant tumour, considered according to the occupations of the deceased persons, the average annual death rate was shown to be highest in those from the asbestos-cement plant (Table 4). The incidence of malignant tumours of the gastrointestinal tract was also studied in that area, using the same methodological approach 5. Some of these tumours had higher rates than expected (data for Croatia as a whole), for example peritoneal tumours in one of the subareas, but also the distribution of oesophageal and pancreatic cancer in the studied area. Tumours of the intestine also showed higher rates than in Croatia as a whole. The rates of primary liver/gall bladder cancer were higher than expected only in the sub-area with a PVC plant. Although not conclusive, these findings might indicate a rôle of environmental exposure to asbestos, including the occurrence of peritoneal mesothelioma. Table 4 - Cumulative number and average annual death rates (per 100,000 inhabitants) due to malignant tumours, by occupation of deceased persons (period ) a Type of industry Average number Number of subjects with Average annual of employees tumours of pharynx, larynx, death rate caused lung and pleura by tumours Asbestos cement plant Cement production Chemical (PVC) industry Construction industry Other a Data relate to 473 deceased persons (out of a total of 1490) obtained by interview from members of families 20

5 M. Šarić: Asbestos-related diseases in Croatia Malignant pleural mesothelioma studies A study investigated patients with pleural mesothelioma treated at the University Hospital in Split between 1995 and : of the 55 patients, 51 were men and 4 women. The average age of the men was 56 (range 38-73) and of the women 53 (range 43-64). In 48 patients (87%), the primary site of the cancer was in the right lung pleura, and in 7 subjects in the left lung pleura. According to work history data, 29 (56.8%) male patients were occupationally exposed to asbestos (asbestos-cement and shipyard workers). Of the 4 women, 3 were occupationally exposed Table 5 - Age-standardized incidence rates of malignant pleural mesothelioma by residence and sex of the patients in Croatia in the period Area Rates/100,000 a Coastal Men 2.66 Women 0.38 Total 1.43 Continental Men 0.69 Women 0.24 Total 0.43 City of Zagreb Men 0.75 Women 0.18 Total 0.42 Total Men 1.34 Women 0.27 Total 0.74 a Goodness-of-fit test for observed rates vs expected rate for Croatia for men p <0.001, chi-square = 14.5, df =2. Post-hoc tests: coastal vs continental p = 0.001, chisquare = 12.3, df = 1; coastal vs city of Zagreb p = 0.035, chi-square = 4.4, df = 1; continental vs city of Zagreb p = 0.905, chi-square = 0.0, df = 1. No statistically significant differences among women from different areas to asbestos, and one was unemployed. The most recent study focussed on the evaluation of actual malignant mesothelioma incidence in the country, its geographical distribution, and the occupations of the patients 7. Data on the incidence of pleural mesothelioma over a seven-year period ( ) were collected from the Croatian Cancer Registry. The tumour incidence for the study period was 0.74 per 100,000. It was higher in men than in women (1.34 vs per 100,000, respectively). Agestandardized incidence rates (per 100,000) by residence showed a significantly uneven geographical distribution for men with the highest rate in the coastal area. In women with mesothelioma, these rates compared by residence were also slightly higher in the coastal area but differences were not statistically significant (Table 5). A short questionnaire was sent to the patients families to gather additional information on their occupation (possible exposure to asbestos), smoking habits, and length of residence. Data were collected by this means on 194 (78.2%) out of 248 patients with mesothelioma. Assuming that the information obtained from the questionnaires on the occupation of the patients was reliable, more than two-thirds of patients with pleural mesothelioma were shown to have been occupationally exposed to asbestos (Table 6). The uneven distribution of the tumour - a higher rate in men in the coastal area - may be related to shipbuilding and other industrial sources of asbestos exposure in that part of the country. Even though the occupation of the remaining third of the patients with pleural mesothelioma was not related to asbestos exposure, the tumour incidence was still about two per million per year. Perhaps this finding might be accounted for by non-occupational exposure to asbestos. It is interesting to note that the difference in age-standardised incidence rates of mesothelioma in men in coastal vs. continental area was statistically much more significant than between the coastal area and Zagreb, which is a relatively big city with 21

6 Eur. J. Oncol. Library, vol. 3 Table 6 - Occupation of patients with pleural mesothelioma, according to the questionnaire data a No. of patients Area Shipbuilding Asbestos Other b Construction Agriculture Other c industry cement industry production Coastal Men Women Total Continental Men Women Total City of Zagreb Men Women Total a Questionnaires were sent to the patients families in Response rate was 78.2%. b Activities involving exposure to asbestos: insulation workers (n = 5), asbestos processing (n = 8), asbestos textile workers (n = 6), transportation and storage of asbestos (n = 6), maintenance and repair of machines and items containing asbestos (n = 4), history of work in asbestos processing plants abroad (n = 4), naval machinists (n = 3), asbestos-cement worker s wife (n = 1). c Blue collar workers (n = 9), technicians (n = 2), administrative staff (n = 10), persons with university education (n = 4), miscellaneous (n = 4), housewives (n = 14). dense traffic and potentially more sources of environmental exposure to asbestos. The importance of working outdoors in areas possibly contaminated by asbestos fibres also deserves consideration. Another study on the epidemiology of malignant pleural mesotheliomas in Croatia (period from 1989 to 1998) was also published in The study was based on data collected and published by the Croatian Cancer Registry. Very recently a 10-year follow-up study on malignant and non-malignant asbestos-related pleural and lung disease performed in the Croatian coastal area was published 9. In this study the emphasis was on the assessment of the risk of developing pleural mesothelioma, in correlation with the duration of exposure to asbestos and the progressive pleural and parenchymal changes. The patients with progressive pleural and parenchymal changes were at particularly high risk of developing malignant pleural mesothelioma. Asbestos consumption and legislation Asbestos has not yet been banned in Croatia. All asbestos used in the country (about 4,000 tonnes/year) is now imported. According to a Government Regulation from the maximum allowable concentrations of asbestos in the working environment are 0.1 fibres/cm 3 for tremolite asbestos, 0.2 fibres/cm 3 for crocidolite and anthophyllite, 0.5 fibres/cm 3 for amosite, and 2 fibres/cm 3 for actinolite and chrysotile asbestos. For all types of asbestos there is a warning that they are proven human carcinogens. Programmes for the surveillance of asbestos-exposed workers are based on the Safety at Work Act and related regulations. They also regulate the requirement for pre-employment screening and periodic health control of workers in workplaces associated with the 22

7 M. Šarić: Asbestos-related diseases in Croatia increased risk of asbestosis, as well as other requirements workers have to meet. The List of Occupational Diseases 11 categorises asbestosis (and related conditions) under Pneumoconioses and/or other diseases caused by fibrogenic mineral dusts. Malignant tumours which might be caused by exposure to asbestos are included in the List under Malignant tumours of several organs and organic systems. The assessment of occupational aetiology is based on algorithms accepted in occupational medicine. Diagnosis includes the following: 1) work history and an assessment of causal relationships between exposure at work and the development of the disease; 2) clinical findings associated with the occurrence of functional and/or morphological impairment of organs or organic systems known to be caused by the related exposure; and 3) results of diagnostic methods verifying such impairment. With the exception of retrospective epidemiological studies described above, there are no regular programmes for the surveillance of people potentially exposed to environmental asbestos. In view of Croatia s intention to join the European Union (EU), there is no doubt it will have to adopt the EU legislation, including the asbestos ban. It has already shown an effort to substitute asbestos in shipyards with other materials and to avoid crocidolite asbestos in the asbestos-cement and asbestos-processing industries. Amphiboles are no longer an issue, except for tremolite asbestos as an impurity of chrysotile. The problem with chrysotile is somewhat different. Although the dose-response relationship has already been established for diseases associated with pure chrysotile such as lung fibrosis, lung cancer, and mesothelioma, no agreement has been achieved on the dose-response curve at low doses. It is known that unit risks (expressed as the increase in lung cancer risk per unit of cumulative exposure) vary widely among different types of exposure to chrysotile asbestos 12. The greatest cancer risk is associated with the production of asbestos textiles. It has been suggested that the risks involved in the production of asbestos-cement, friction materials, and chrysotile mining may be lower. As chrysotile textile contains higher proportions of very long fibres than does the chrysotile to which miners and other lower risk groups are exposed, the carcinogenicity of chrysotile fibres may be directly related to their length, that is if it exceeds 10 to 20 μm. Asbestos fibre types seem to influence the incidence of malignant mesothelioma as well. In any case, there are reasons to believe that the dose-response relationship for chrysotile is a threshold phenomenon 13. In a recent article, Valić 14 questions the scientific justification for the EU ban of all types of asbestos and raises a practical question: should Croatia pass a phase-out rule on asbestos to be applied by the year 2005 (EU enforcement deadline), although it will not have become a member of the EU by that time? The crucial issue for all of us at this point, however, is the potential harmfulness of substances being introduced as asbestos substitutes. References 1. Zorica M, Šarić M. Asbestosis in a manufacture of asbestos-cement products (in Croatian). Arh Hig Rada Toksikol 1961; 12: Deèkovic-Vukres V, Hemen M. Asbestosis as occupational disease in Croatia (period ) (in Croatian). Simpozij o azbestozi i drugim azbestom izazvanim bolestima, Split 27. i 28. rujna Zbornik priopænja i radova, Split: Klinièka bolnica i Zavod za javno zdravstvo županije splitsko-dalmatinske, 2001: Šarić M, Vujović M. Malignant tumours in an area with an asbestos processing plant. Public Health Rev 1994; 22:

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